From white to brown – and the role of insulin

Abstract

Obesity and its consequences, such as insulin resistance and metabolic syndrome, is increasing in importance, its prevalence reaching 35% of adults being overweight and 11% obese. The recent discovery of thermogenically active adipose tissue in adult humans, which is able to dissipate excess energy creating heat, has drawn attention to research on brown adipose tissue as well as so called brite adipocytes, that arise in white adipose depots upon cold exposure. A question of interest is whether thermogenically active adipose tissue differs from white fat regarding insulin sensitivity or vice versa depends on functional insulin signalling for development and function. While it had recently been shown that the development of brown fat depends on insulin, however that it maintains sensitivity to β3-adrenergic stimulation in the absence of insulin signaling, the role of insulin in browning of white depots is less clear. We show here that both absence of and resistance to insulin lead to lowered brite state in WAT, but β3-adrenergic stimulation could completely rescue this defect. Further we investigated whether the brite state leads to enhanced insulin sensitivity, which would render browning of WAT an interesting tool for counteracting metabolic consequences of obesity. We showed that indeed brite adipocytes and browned WAT tissues exhibit elevated glucose uptake. However we proved that neither isolated adipocytes differentiated into brite cells nor browned WAT were more insulin sensitive than white. Overall we conclude that while browning is efficient in enhancing systemic glucose clearance, it does not render adipose tissue more insulin sensitive.